Miscellaneous Fungal Diseases

Chapter 68

Miscellaneous Fungal Diseases

In contrast to the well-recognized fungal pathogens that cause endemic mycoses (such as Blastomyces, Histoplasma, and Cryptococcus), miscellaneous fungal pathogens comprise large groups of fungi with unfamiliar names that traditionally have caused disease only sporadically. These opportunistic fungi have low inherent virulence and typically cause infection only when normal host resistance mechanisms are compromised. Over the past 30 years, these opportunists have become increasingly important in human patients because immunocompromise associated with chemotherapy, organ transplantation, and HIV infection has become more prevalent. Similarly, over the past 5 to 10 years, the frequency with which opportunistic fungal infections are encountered in small animal patients has increased significantly in association with the use of multiagent immunosuppressive therapy (especially with cyclosporine) to treat immune-mediated disease in dogs. Thus, veterinarians are increasingly likely to encounter patients infected by an opportunistic fungal pathogen with which they are unfamiliar.

Unlike the common endemic fungal pathogens (for which a definitive diagnosis can often be made simply by visualizing the unique morphologic features of the organism in cytologic or histologic samples), opportunistic fungi can only be identified to genus and species level by culture or molecular methods. However, they can be assigned to categories based on their morphologic features in tissue, such as pigmentation, hyphal diameter, and frequency of septation. These categories include phaeohyphomycosis (pigmented hyphal or yeast forms), hyalohyphomycosis (nonpigmented hyphal forms), eumycotic mycetoma (fibrosing granuloma with black or white tissue grains consisting of aggregates of pigmented or nonpigmented fungi, respectively), and zygomycosis (wide, infrequently septate, nonpigmented hyphae associated with pyogranulomatous and eosinophilic inflammation). Because of its similarities to pythiosis and lagenidiosis, zygomycosis is discussed in Chapter 69. Although identification of a specific pathogen after culture is ideal, classification of opportunistic mycoses based on the categories just listed is usually sufficient to allow the clinician to make a reasonable prediction about clinical course and prognosis and to make appropriate treatment decisions. Because many opportunistic fungi are common contaminants and can normally be found on skin, nasal mucosa, and other nonsterile sites, culture- or PCR-based identification of a potential opportunistic fungal pathogen from a skin specimen, nasal swab, or exudate should not be considered evidence of fungal infection unless there is supportive histologic or cytologic evidence of tissue invasion by a morphologically compatible organism.


Etiology and Epidemiology

The term “phaeohyphomycosis” refers to cutaneous, subcutaneous, cerebral, or disseminated infections caused by pigmented (also known as dematiaceous) fungi that contain melanin in their cell walls.1 Infection usually results from cutaneous inoculation. Fungal genera that have been identified as agents of phaeohyphomycosis in veterinary patients include Alternaria, Bipolaris, Cladophialophora, Curvularia, Exophiala, Fonsecaea, Moniliella, Phialophora, Ramichloridium, Ulocladium, and Scolecobasidium, among others (Table 68-1).

TABLE 68-1

Causative Agents and Histologic/Cytologic Characteristics Associated with Miscellaneous Fungal and Pseudofungal Pathogens

Disease Causative Agents Histologic and Cytologic Characteristics
Phaeohyphomycosis Alternaria, Bipolaris, Phialophora, Cladophialophora (Cladosporium), Curvularia, Exophiala, Fonsecaea, Moniliella, Ochroconis, Ramichloridium, others Pyogranulomatous inflammation associated with pigmented, irregularly septate hyphae or yeast-like cells that may be solitary or may cluster in small groups or chains
Hyalohyphomycosis Acremonium, Fusarium, Geotrichum, Geosmithia, Paecilomyces, Phialosimplex, Pseudallescheria, Sagenomella, Scedosporium, Schizophyllum, others Pyogranulomatous inflammation associated with hyphal elements that have nonpigmented (transparent, hyaline) walls; Phialosimplex may cause yeast-like forms in tissue
Curvularia Pyogranulomatous inflammation associated with aggregates of pigmented fungal organisms (which appear grossly as pigmented tissue grains)
Pseudallescheria boydii, Acremonium Pyogranulomatous inflammation associated with aggregates of nonpigmented fungal organisms (which appear grossly as nonpigmented tissue grains)
Pythiosis Pythium insidiosum Pyogranulomatous and eosinophilic inflammation associated with broad (2-7 µm), infrequently septate hyphae (see Chapter 69)
Lagenidiosis Lagenidium Pyogranulomatous and eosinophilic inflammation associated with broad (4-25 µm), infrequently septate hyphae (see Chapter 69)
Zygomycosis Conidiobolus spp., Basidiobolus ranarum in dogs; Rhizomucor, Mucor, and Cokeromyces in cats Pyogranulomatous and eosinophilic inflammation associated with broad (5-20 µm), infrequently septate hyphae with thick prominent eosinophilic sleeve (see Chapter 69)
Aspergillosis Aspergillus terreus, A. deflectus, A. flavipes, A. fumigatus, others Suppurative to granulomatous inflammation associated with multiple, nonpigmented, 3- to 6-µm, septate hyphae with parallel walls and 45-degree angle branching (see Chapter 65)
Candidiasis Candida albicans, other Candida spp. Suppurative inflammation with numerous 2- to 6-µm oval yeasts, pseudohyphae (chains of oval yeast cells), and true hyphae (see Chapter 67)

Clinical Features

The most common clinical manifestations of phaeohyphomycosis in immunocompetent small animals are lesions associated with the digits, pinnae, nasal planum, or nasal cavity in cats (Figure 68-1). 28 Cutaneous lesions occur less often in dogs.9 In addition, granulomatous meningoencephalitis caused by pigmented fungi (especially Cladophialophora bantiana) have been described both in dogs and cats.1014 In immunocompromised patients, the most common presentation appears to be multifocal cutaneous lesions in dogs treated with multiagent immunosuppressive therapy, especially that which includes cyclosporine.1517

Animals with phaeohyphomycosis typically have cutaneous nodules or a visible nasal mass. Infected tissues may appear grossly pigmented, and thus masses may be confused with melanomas. Phaeohyphomycoses tend to be locally invasive and may extend to involve regional lymph nodes (Figure 68-2). Systemic dissemination more often occurs in animals treated with immunosuppressive drugs, but disseminated infections have also been described in apparently immunocompetent patients.18,19 Animals with central nervous system (CNS) phaeohyphomycosis may have neurologic signs such as obtundation, seizures, abnormal placing reactions, circling, tremors, ataxia, and abnormal cranial nerve function.


Laboratory and Imaging Abnormalities

Results of a CBC, biochemistry panel, and urinalysis in animals with cutaneous phaeohyphomycoses are typically unremarkable. Animals with disseminated disease can have abnormalities associated with underlying immunosuppressive illness or drug treatment. Imaging with computed tomography (CT) or MRI in animals with CNS involvement may reveal focal or multifocal contrast-enhancing lesions that may be associated with hydrocephalus (Figure 68-3).

Cytologic and Histologic Findings

On histologic or cytologic examination, fungi that cause phaeohyphomycosis appear as dark-walled, irregularly septate hyphae or as yeast-like cells, solitary or in small groups or chains (Figure 68-4). Pigmentation may not always be apparent on cytologic examination (Figure 68-5). The presence of melanin in the walls of lightly-pigmented hyphae can be confirmed by the examination of unstained sections, by lowering the microscope condenser during examination, or by utilization of a Fontana-Masson stain for melanin.

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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Miscellaneous Fungal Diseases

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